2-C-Hydroxy­methyl-2,3-O-isopropyl­idene-3-C-methyl-β-L-erythrose

The relative configuration of the title compound, C₉H₁₆O₅, has been firmly established by X-ray crystallographic analysis. The absolute configuration of this sugar was determined by the use of 2-C-methyl-D-ribono-1,4-lactone as the starting material. The structure exists as a hydrogen-bonded network, with each mol­ecule being a donor and an acceptor for two hydrogen bonds.

Key indicators

• Single-crystal X-ray study
• T = 150 K
• Mean [sigma](C-C) = 0.003 Å
• R factor = 0.031
• wR factor = 0.074
• Data-to-parameter ratio = 10.5

checkCIF/PLATON results

No syntax errors found



Alert level G
REFLT03_ALERT_4_G Please check that the estimate of the number of Friedel pairs is
            correct. If it is not, please give the correct count in the
            _publ_section_exptl_refinement section of the submitted CIF.
           From the CIF: _diffrn_reflns_theta_max           27.48
           From the CIF: _reflns_number_total               1329
           Count of symmetry unique reflns         1345
           Completeness (_total/calc)             98.81%
           TEST3: Check Friedels for noncentro structure
           Estimate of Friedel pairs measured         0
           Fraction of Friedel pairs measured     0.000
           Are heavy atom types Z>Si present         no
PLAT791_ALERT_1_G Confirm the Absolute Configuration of C1     = .          S
PLAT791_ALERT_1_G Confirm the Absolute Configuration of C2     = .          S
PLAT791_ALERT_1_G Confirm the Absolute Configuration of C10    = .          S

   0 ALERT level A = In general: serious problem
   0 ALERT level B = Potentially serious problem
   0 ALERT level C = Check and explain
   4 ALERT level G = General alerts; check

   3 ALERT type 1 CIF construction/syntax error, inconsistent or missing data
   0 ALERT type 2 Indicator that the structure model may be wrong or deficient
   0 ALERT type 3 Indicator that the structure quality may be low
   1 ALERT type 4 Improvement, methodology, query or suggestion
   0 ALERT type 5 Informative message, check

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S1. Comment

Singly branched sugars have been found in nature and their occurrence has prompted interest in their synthesis and biological evaluation (Chapleur & Chrétien, 1997). For example, 2-C-substituted mannose derivatives have been shown to have therapeutic potential (Mitchell et al., 2007). The Kiliani reaction of ketoses with cyanide (Hotchkiss et al., 2006, Soengas et al., 2005) and calcium oxide treatment of Amadori compounds have proved to be valuable routes towards branched sugars (Hotchkiss et al., 2006, 2007). In addition the Aldol reaction using formaldehyde and potassium carbonate can be used to introduce hydroxymethyl branches to sugars, for example in the synthesis of hamamalose (Ho, 1978) and apiose (Koos & Mosher, 1986).

Sugars containing more than one branch are very rare. Examples of sugars that contain two carbon branches include 2,4-dimethyl-3,4-O-isopropylidene-L-arabinono-1,5-lactone (Booth, Watkin et al., 2007) and various protected forms of 3,5-di-C-methyl-mannono and glucono lactone (Booth et al., 2007a, 2007b, 2007c). 2,3-C-Dimethyl-D-allono-1,4-lactone (Jones et al., 2007) is an example of a sugar with adjacent branching centres.

The crystal structure of the title compound (Fig. 1) exists as a three dimensionally hydrogen bonded lattice with each molecule being both a donor and an acceptor for two hydrogen bonds (Fig. 2).

Related literature

For related literature, see: Booth et al. (2007a,b,c); Booth, Best et al. (2007); Booth, Watkin et al. (2007); Chapleur & Chrétien (1997); Ho (1978); Hotchkiss et al. (2006, 2007); Jones et al. (2007); Koos & Mosher (1986); Mitchell et al. (2007); Soengas et al. (2005).

S2. Experimental

Protected 3-C-methyl-L-erythrose (Booth, Best et al., 2007) 2, derived from 2-C-methyl-D-ribono-1,4-lactone 1, was treated with potassium carbonate and an excess of formaldehyde (Fig. 3). This gave a single product 3, a mixture of anomers in solution, which was found to crystallize as the pure β form (Fig. 1). The title compound was recrystallized from methanol; m.p. 337–343 K; [α]_D²¹ +66.2 (c, 1.34 in acetone).

S3. Refinement

In the absence of significant anomalous scattering, Friedel pairs were merged and the absolute configuration was assigned on the basis of the starting material.

The H atoms were all located in a difference map, but those attached to carbon atoms were repositioned geometrically. The H atoms were initially refined with soft restraints on the bond lengths and angles to regularize their geometry (C—H in the range 0.93–0.98, O—H = 0.82 Å) and U_iso(H) (in the range 1.2–1.5 times U_eq of the parent atom), after which the positions were refined with riding constraints.

Computing details

Data collection: COLLECT (Nonius, 2001); cell refinement: DENZO/SCALEPACK (Otwinowski & Minor, 1997); data reduction: DENZO/SCALEPACK; program(s) used to solve structure: SIR92 (Altomare et al., 1994); program(s) used to refine structure: CRYSTALS (Betteridge et al., 2003); molecular graphics: CAMERON (Watkin et al., 1996); software used to prepare material for publication: CRYSTALS.

Figures

	Fig. 1. The molecular structure of the title compound with displacement ellipsoids drawn at the 50% probability level. H atoms are shown as spheres of arbitary radius.
	Fig. 2. Packing of the title compound projected along the a-axis. Hydrogen bonds are shown as dotted lines.
	Fig. 3. The reaction scheme.

2-C-Hydroxymethyl-2,3-O-isopropylidene-3-C-methyl- β-L-erythrose

Crystal data

C9H16O5	F(000) = 440
Mr = 204.22	Dx = 1.363 Mg m^−3
Orthorhombic, P212121	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2ac 2ab	Cell parameters from 1304 reflections
a = 6.2840 (2) Å	θ = 5–27°
b = 11.2043 (3) Å	µ = 0.11 mm^−1
c = 14.1345 (5) Å	T = 150 K
V = 995.18 (5) Å^3	Plate, colourless
Z = 4	0.40 × 0.15 × 0.15 mm

Data collection

Nonius KappaCCD area-detector diffractometer	1174 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.030
ω scans	θmax = 27.5°, θmin = 5.4°
Absorption correction: multi-scan (DENZO/SCALEPACK; Otwinowski & Minor, 1997)	h = −8→8
Tmin = 0.89, Tmax = 0.98	k = −14→14
6798 measured reflections	l = −18→18
1329 independent reflections

Refinement

Refinement on F^2	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Hydrogen site location: inferred from neighbouring sites
R[F^2 > 2σ(F^2)] = 0.031	H-atom parameters constrained
wR(F^2) = 0.074	w = 1/[σ^2(F^2) + (0.04P)^2 + 0.26P], where P = [max(Fo^2,0) + 2Fc^2]/3
S = 0.94	(Δ/σ)max = 0.000331
1329 reflections	Δρmax = 0.23 e Å^−3
127 parameters	Δρmin = −0.21 e Å^−3
0 restraints

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Ų)

	x	y	z	Uiso*/Ueq
C1	0.4004 (3)	0.62732 (15)	0.82157 (12)	0.0170
C2	0.4011 (3)	0.48976 (15)	0.80312 (11)	0.0175
O3	0.4963 (2)	0.47844 (10)	0.71058 (7)	0.0207
C4	0.5033 (3)	0.59116 (14)	0.66416 (11)	0.0192
O5	0.4968 (2)	0.67791 (10)	0.73859 (8)	0.0190
C6	0.3161 (4)	0.60448 (18)	0.59812 (14)	0.0310
C7	0.7142 (3)	0.60183 (18)	0.61403 (15)	0.0297
C8	0.5634 (3)	0.44334 (16)	0.87399 (12)	0.0220
O9	0.70020 (19)	0.54266 (11)	0.89385 (8)	0.0226
C10	0.5609 (3)	0.64203 (16)	0.90340 (11)	0.0194
O11	0.4474 (2)	0.63675 (12)	0.98858 (8)	0.0255
C12	0.1885 (3)	0.42543 (16)	0.80539 (13)	0.0238
C13	0.1860 (3)	0.68450 (15)	0.83936 (13)	0.0203
O14	0.2049 (2)	0.80853 (11)	0.86261 (9)	0.0251
H61	0.3262	0.6813	0.5628	0.0499*
H62	0.3133	0.5390	0.5506	0.0503*
H63	0.1852	0.6027	0.6356	0.0507*
H71	0.7202	0.6830	0.5847	0.0470*
H72	0.7185	0.5393	0.5626	0.0469*
H73	0.8304	0.5901	0.6610	0.0479*
H81	0.6440	0.3754	0.8455	0.0286*
H82	0.4869	0.4191	0.9330	0.0282*
H101	0.6441	0.7203	0.8990	0.0242*
H121	0.2147	0.3398	0.7899	0.0380*
H122	0.0922	0.4610	0.7571	0.0387*
H123	0.1219	0.4341	0.8684	0.0382*
H131	0.0965	0.6764	0.7798	0.0269*
H132	0.1112	0.6441	0.8918	0.0265*
H15	0.5366	0.6493	1.0330	0.0412*
H16	0.3095	0.8395	0.8319	0.0416*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
C1	0.0193 (8)	0.0180 (8)	0.0137 (8)	−0.0014 (7)	0.0007 (6)	0.0000 (6)
C2	0.0204 (8)	0.0182 (8)	0.0137 (7)	−0.0005 (7)	0.0018 (7)	−0.0017 (7)
O3	0.0293 (7)	0.0176 (6)	0.0152 (5)	0.0020 (6)	0.0051 (6)	−0.0006 (4)
C4	0.0256 (8)	0.0166 (8)	0.0154 (7)	0.0007 (8)	0.0009 (8)	−0.0020 (6)
O5	0.0253 (6)	0.0170 (5)	0.0148 (5)	−0.0015 (6)	0.0035 (5)	−0.0010 (4)
C6	0.0360 (11)	0.0342 (11)	0.0226 (9)	−0.0004 (10)	−0.0090 (10)	−0.0014 (9)
C7	0.0348 (11)	0.0248 (10)	0.0294 (10)	−0.0024 (9)	0.0138 (9)	−0.0023 (8)
C8	0.0253 (9)	0.0191 (8)	0.0216 (9)	−0.0010 (8)	−0.0020 (8)	−0.0004 (7)
O9	0.0180 (6)	0.0251 (6)	0.0247 (6)	0.0002 (6)	−0.0043 (6)	−0.0013 (5)
C10	0.0195 (8)	0.0219 (8)	0.0168 (8)	−0.0026 (8)	−0.0017 (7)	−0.0028 (7)
O11	0.0274 (7)	0.0331 (7)	0.0161 (6)	−0.0020 (6)	−0.0005 (5)	−0.0037 (5)
C12	0.0225 (9)	0.0204 (8)	0.0285 (9)	−0.0034 (8)	−0.0001 (8)	−0.0015 (8)
C13	0.0197 (8)	0.0191 (8)	0.0220 (8)	0.0000 (7)	0.0015 (7)	−0.0022 (7)
O14	0.0284 (7)	0.0176 (6)	0.0294 (7)	0.0011 (6)	0.0115 (6)	−0.0030 (5)

Geometric parameters (Å, º)

C1—C2	1.563 (2)	C7—H73	0.996
C1—O5	1.437 (2)	C8—O9	1.434 (2)
C1—C10	1.543 (2)	C8—H81	0.999
C1—C13	1.513 (2)	C8—H82	1.000
C2—O3	1.4439 (19)	O9—C10	1.423 (2)
C2—C8	1.522 (2)	C10—O11	1.400 (2)
C2—C12	1.518 (2)	C10—H101	1.023
O3—C4	1.4240 (19)	O11—H15	0.854
C4—O5	1.4329 (19)	C12—H121	0.998
C4—C6	1.509 (3)	C12—H122	0.996
C4—C7	1.507 (3)	C12—H123	0.989
C6—H61	0.997	C13—O14	1.433 (2)
C6—H62	0.996	C13—H131	1.017
C6—H63	0.978	C13—H132	0.987
C7—H71	1.001	O14—H16	0.861
C7—H72	1.010
C2—C1—O5	104.58 (13)	H71—C7—H73	111.6
C2—C1—C10	103.22 (14)	H72—C7—H73	111.6
O5—C1—C10	107.11 (13)	C2—C8—O9	105.41 (14)
C2—C1—C13	116.58 (15)	C2—C8—H81	109.6
O5—C1—C13	110.13 (14)	O9—C8—H81	111.5
C10—C1—C13	114.34 (13)	C2—C8—H82	108.6
C1—C2—O3	103.82 (13)	O9—C8—H82	109.6
C1—C2—C8	103.23 (14)	H81—C8—H82	111.9
O3—C2—C8	106.76 (14)	C8—O9—C10	104.90 (12)
C1—C2—C12	117.54 (16)	C1—C10—O9	104.32 (13)
O3—C2—C12	110.00 (14)	C1—C10—O11	107.89 (13)
C8—C2—C12	114.44 (14)	O9—C10—O11	111.21 (14)
C2—O3—C4	110.63 (12)	C1—C10—H101	112.3
O3—C4—O5	105.21 (12)	O9—C10—H101	110.5
O3—C4—C6	110.40 (15)	O11—C10—H101	110.4
O5—C4—C6	111.41 (15)	C10—O11—H15	107.0
O3—C4—C7	108.31 (15)	C2—C12—H121	107.9
O5—C4—C7	108.43 (15)	C2—C12—H122	109.3
C6—C4—C7	112.75 (14)	H121—C12—H122	109.6
C1—O5—C4	110.11 (12)	C2—C12—H123	110.2
C4—C6—H61	110.2	H121—C12—H123	111.2
C4—C6—H62	111.0	H122—C12—H123	108.7
H61—C6—H62	107.5	C1—C13—O14	112.02 (14)
C4—C6—H63	108.6	C1—C13—H131	108.5
H61—C6—H63	110.0	O14—C13—H131	108.8
H62—C6—H63	109.6	C1—C13—H132	110.8
C4—C7—H71	107.5	O14—C13—H132	108.1
C4—C7—H72	107.9	H131—C13—H132	108.5
H71—C7—H72	109.3	C13—O14—H16	109.8
C4—C7—H73	108.8

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
O11—H15···O14^i	0.85	1.88	2.724 (2)	172
O14—H16···O3^ii	0.86	2.07	2.867 (2)	154

Symmetry codes: (i) x+1/2, −y+3/2, −z+2; (ii) −x+1, y+1/2, −z+3/2.